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Receptor molecules with large cavities synthesized by the combination of building blocks that already possess a cavity, viz. calix[4]arenes and resorcin[4]arenes, are described. These receptor molecules are synthesized by reaction of one or two upper rim 1,2-difunctionalized calix[4]arene fragments oriented either endo or exo toward a cavitand unit. The endo:exo ratio depends on the substituents at the 3- and 4-positions of the calix[4]arenes. These novel receptor molecules complex steroids with association constants of (0.9−9.5) × 102 M-1 in CDCl3.

Resorcin[4]arene tetracarboxylic acids 5,6 (A) and resorcin[4]arene tetrapyridines 2,3 (P) self‐assemble in chloroform solution to form stable heterotopic AP dimers. Data from NMR titration and dilution experiments, as well as from vapor‐pressure osmometry (VPO), indicate that the AP dimer is formed with an association constant greater than 107 M−1. Solid‐solution extraction experiments are indicative of the formation of a 2:1 trimer (A2P), while self‐associated homotopic species (A2 and A3) can be detected by NMR and VPO. Analysis of the heterotopic noncovalent assembly process over a range of compositions shows that these other species are much less stable than the AP heterodimer, which is the exclusive species at an A/P concentration ratio of 1:1 (> 99.7% of the total at 10 mM).

Receptor molecules with a preorganized cavity were synthesized by combining two resorcin [4]arene and one calix[4]-arene building block. Based on predictions from a computational study which matches hosts and guests, several steroids, sugar derivatives, and alkaloids were selected for complexation studies. Experimentally the complexation of such guests by these receptor molecules was proven by 'H-NMR spectroscopy (association constants of 1.0-6.0 X 10' M-' in CDC1,). One of these receptors with four hydroxyl groups forms a dimeric capsule (Kdlmer = 11 M -~ in CDC13). Evidence for this dimerization comes from 'H-NMR, FAB MS spectroscopy, and molecular mechanics and dynamics calculations.Nowadays a large variety of synthetic hosts for relatively small guest species e.g. cations, anions, and small neutral molecules are described in the literature. In most cases the general strategy focuses on the complementarity of functional groups in receptor and guest; this approach is always guest-directed and requires for each individual guest a new synthetic pathway. With increasing size and structural complexity of the guest species, this approach becomes increasingly demanding in terms of design and the number of steps in the synthesis of a complementary host (or receptor) molecule.An alternative approach to the synthesis of such receptor molecules is based on the proper combination of (different) molecular building blocks to which functional groups can be attached, giving rise to molecules with large well-defined cavities and hydrophobic surfaces. Most likely, the complexation of large guest molecules requires preorganized host molecules because otherwise the entropy might be too high to form an appropriate cavity. On the other hand, some flexibility gives the host molecules the possibility for structural adaption that might be necessary for complexation. Computational methods for matching the shape of host and guest are nowadays available ['].More or less planar building blocks that have recently been used in the design of receptor for the complexation of small neutral molecules and spherical anions are porphyrin~ [~] andIn our own work we use mainly non-planar building blocks that have a molecular cavity and a variety of functional groups e.g. calix [4] ["]. A systematic search for suitable guests using the computer simulation program DOCK['] revealed among others a good fit for different steroids, aromatic compounds, sugar derivatives, and fused ring systems. Unfortunately, in CDC13 solution complexation could not be detected probably because the cavity is too well solvated. Therefore, we have synthesized the more flexible combination of two upper rim 1,2-difunctionalized calix[4]arenes coupled to one resorcin[4]arene (1, 2, and 3, see Scheme 1). These compounds complex steroids (corticosteroids) in non-uqueous media with association constants of 0.9-9.5 X 102 M -~ in CDC13 ['21.In this paper we describe the synthesis of molecules 4 and 5 (see Scheme 2) that are constructed by the combination of two resorcin [4]

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